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First published online July 18, 2008
Experimental Biology and Medicine 233:1309-1314 (2008)
doi: 10.3181/0803-RM-85
© 2008 by the Society for Experimental Biology and Medicine

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ORIGINAL RESEARCH ARTICLE

Regulation of Mammary Gland Sensitivity to Thyroid Hormones During the Transition from Pregnancy to Lactation

A. V. Capuco1, E. E. Connor and D. L. Wood

Bovine Functional Genomics Laboratory, USDA-ARS, Beltsville, Maryland 20705

To whom requests for reprints should be addressed at 1 Bovine Functional Genomics Laboratory, USDA-ARS, Building 200, Room 14 Powder-Mill Road, BARC-East, Beltsville, MD 20705. E-mail: tony.capuco{at}ars.usda.gov

Thyroid hormones are galactopoietic and help to establish the mammary gland’s metabolic priority during lactation. Expression patterns for genes that can alter tissue sensitivity to thyroid hormones and thyroid hormone activity were evaluated in the mammary gland and liver of cows at 53, 35, 20, and 7 days before expected parturition, and 14 and 90 days into the subsequent lactation. Transcript abundance for the three isoforms of iodothyronine deiodinase, type I (DIO1), type II (DIO2) and type III (DIO3), thyroid hormone receptors alpha1 (TR{alpha}1), alpha2 (TR{alpha}2) and beta1 (TRβ1), and retinoic acid receptors alpha (RXR{alpha}) and gamma (RXR{gamma}), which act as coregulators of thyroid hormone receptor action, were evaluated by quantitative RT-PCR. The DIO3 is a 5-deiodinase that produces inactive iodothyronine metabolites, whereas DIO1 and DIO2 generate the active thyroid hormone, triiodothyronine, from the relatively inactive precursor, thyroxine. Low copy numbers of DIO3 transcripts were present in mammary gland and liver. DIO2 was the predominant isoform expressed in mammary gland and DIO1 was the predominant isoform expressed in liver. Quantity of DIO1 mRNA in liver tissues did not differ with physiological state, but tended to be lowest during lactation. Quantity of DIO2 mRNA in mammary gland increased during lactation (P < 0.05), with copy numbers at 90 days of lactation 6-fold greater than at 35 and 20 days prepartum. When ratios of DIO2/DIO3 mRNA were evaluated, the increase was more pronounced (>100-fold). Quantity of TRβ1 mRNA in mammary gland increased with onset of lactation, whereas TR{alpha}1 and TR{alpha}2 transcripts did not vary with physiological state. Conversely, quantity of RXR{alpha} mRNA decreased during late gestation to low levels during early lactation. Data suggest that increased expression of mammary TRβ1 and DIO2, and decreased RXR{alpha}, provide a mechanism to increase thyroid hormone activity within the mammary gland during lactation.

Key Words: iodothyronine deiodinase • thyroid hormone receptor • thyroid hormone • lactogenesis • retinoid receptor







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